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Novel Targeted Liposomes Deliver siRNA to Hepatocellular Carcinoma Cells in vitro
Author(s) -
Dorasamy Shantal,
Narainpersad Nicolisha,
Singh Moganavelli,
Ariatti Mario
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01446.x
Subject(s) - asialoglycoprotein receptor , small interfering rna , transfection , liposome , rna , cationic liposome , chemistry , microbiology and biotechnology , in vitro , biology , biophysics , biochemistry , hepatocyte , gene
Liposomes form a major class of non‐viral vectors for short interfering RNA delivery, however tissue and cell‐specific targeting are additional requirements in the design of short interfering RNA delivery systems with a therapeutic potential. Selective delivery of liposomes to hepatocytes may be achieved by directing complexes to the asialoglycoprotein receptor, which is expressed on hepatocytes, and which displays high affinity for the β‐ d ‐galactopyranosyl moiety. We aimed to show that the d ‐galactopyranosyl ring in direct β‐glycosidic link to cholesterol, when formulated into liposomes with 3β[ N ‐( N ′, N ′‐dimethylaminopropane) carbamoyl] cholesterol (Chol‐T) or its quaternary trimethylammonium analogue (Chol‐Q), may promote targeted delivery of cytotoxic short interfering RNA to the human hepatoma cell line HepG2 via the asialoglycoprotein receptor. Liposome‐short interfering RNA interactions were characterized by electron microscopy, dye displacement, gel retardation and nuclease assays. Stable short interfering RNA‐protective lipoplexes were formed at N/P ratios in the range 5:1–7:1. Targeted lipoplex 4 achieved high transfection efficiencies at 50 n m short interfering RNA (70%) and <10% in a competition assay, whilst untargeted complexes reached low levels at the same concentration (<25%). Transfection efficiencies of all lipoplexes in the asialoglycoprotein receptor‐negative cell line HEK293 under the same conditions were low. Lipoplexes containing cholesteryl‐β‐ d ‐galactopyranoside may therefore form the basis for the development of useful hepatotropic short interfering RNA delivery vectors.